Non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are major causes of morbidity and mortality, with many patients not achieving cure. Monoclonal antibody-based therapies have been demonstrated to improve outcomes in some settings, and agents targeting novel antigens offer therapeutic promise. CD74 is widely expressed on B cell and other tumors, and has been associated with cellular proliferation and survival. The humanized anti-CD74 monoclonal antibody hLL1 has been evaluated in preclinical studies and demonstrated to induce a variety of anti-proliferative effects. We propose to evaluate this agent for potential therapeutic use in patients with B cell malignancies. Specifically, we plan to: Determine the phase I safety and activity (and establish a phase II dose) of the anti- CD74 humanized monoclonal antibody hLL1 in patients with recurrent NHL and CLL; Evaluate the in vivo biodistribution of Indium-111-labeled hLL1 in patients with B cell malignancies, and perform exploratory correlations with serum pharmacokinetics, tumor immunohistochemistry and lymphoma response. We anticipate that this project will provide important information regarding the potential utility of CD74-directed immunotherapy in B cell malignancies and possibly other tumor types, and will lead to further study of this approach on a broader scale which will hopefully improve outcomes for patients with these malignancies. [unreadable] [unreadable] [unreadable]